317- What is the importance of family history in the differential diagnosis of DSD?
Family history provides important clues in the differential diagnosis of DSD as
summarized in the table given below.History Etiology
Consanguinity Congenital adrenal hyperplasia
5 α-reductase type 2 defi ciency
Androgen biosynthetic defects
Gonadal dysgenesis
Maternal virilization during pregnancy Placental aromatase defi ciency
P450 oxidoreductase defi ciency
Neonatal deaths CAH with salt crises
Precocious puberty (heterosexual or isosexual) CAH
Primary amenorrhea Androgen insensitivity syndrome
Gonadal dysgenesis
CAH due to 17α-hydroxylase defi ciency
Gynecomastia Androgen insensitivity syndrome
Androgen biosynthetic defects
Advanced maternal age Turner syndrome
Klinefelter syndrome- What are the DSDs which present without genital ambiguity?
46,XY DSDs which do not manifest with genital ambiguity include CAIS,
Swyer syndrome (46,XY complete gonadal dysgenesis), and, rarely, severe
17 α-hydroxylase defi ciency. Patients with these disorders have female exter-
nal genitalia. In addition, patients with congenital anorchia (vanishing testes
syndrome) present with bilateral non-palpable gonads, with unambiguous
male external genitalia. 46,XX DSDs which can present with apparently
male genitalia without any genital ambiguity include CAH due to
21 α-hydroxylase and 11β-hydroxylase defi ciency, SRY gene translocation,
SOX9 duplications, and RSPO1-inactivating mutations. Patients with CAH
can present with apparently normal male external genitalia without palpable
gonads, whereas the latter disorders are associated with normal male exter-
nal genitalia and palpable gonads. In addition, Turner syndrome and
Klinefelter are the sex chromosomal DSDs that present without genital
ambiguity.9 Disorders of Sex Development